-
Journal of Ethnopharmacology Aug 2017Mitragyna speciosa (Korth.) Havil. (M. speciosa) is among the most well-known plants used in ethnic practice of Southeast Asia. It has gained increasing attention as a...
Effects of alkaloid-rich extract from Mitragyna speciosa (Korth.) Havil. on naloxone-precipitated morphine withdrawal symptoms and local field potential in the nucleus accumbens of mice.
ETHNOPHARMACOLOGICAL RELEVANCE
Mitragyna speciosa (Korth.) Havil. (M. speciosa) is among the most well-known plants used in ethnic practice of Southeast Asia. It has gained increasing attention as a plant with potential to substitute morphine in addiction treatment program. However, its action on the central nervous system is controversial.
AIM OF THE STUDY
This study investigated the effects of M. speciosa alkaloid extract on naloxone-precipitated morphine withdrawal and neural signaling in the nucleus accumbens (NAc, brain reward center) of mice.
MATERIALS AND METHODS
The effects of M. speciosa alkaloid extract and mitragynine, a pure major constituent, on naloxone-precipitated morphine withdrawal were examined. Male Swiss Albino (ICR) mice were rendered dependent on morphine before injection with naloxone, a nonspecific opioid antagonist, to induce morphine withdrawal symptoms. The intensity of naloxone-precipitated morphine withdrawal was assessed from jumping behavior and diarrhea induced during a period of morphine withdrawal. To test possible addictive effect of M. speciosa alkaloid extract, mice were implanted with intracranial electrode into the NAc for local field potential (LFP) recording. Following M. speciosa alkaloid extract (80mg/kg) and morphine (15mg/kg) treatment, LFP power spectra and spontaneous motor activity were analyzed in comparison to control levels.
RESULTS
One-way ANOVA and multiple comparisons revealed that M. speciosa alkaloid extract (80 and 100mg/kg) significantly decreased the number of jumping behavior induced by morphine withdrawal whereas mitragynine did not. Additionally, M. speciosa alkaloid extract significantly decreased dry and wet fecal excretions induced by morphine withdrawal. LFP analysis revealed that morphine significantly decreased alpha (9.7-12Hz) and increased low gamma (30.3-44.9Hz) and high gamma (60.5-95.7Hz) powers in the NAc whereas M. speciosa alkaloid extract did not. Spontaneous motor activity was significantly increased by morphine but not M. speciosa alkaloid extract.
CONCLUSIONS
Taken together, M. speciosa alkaloid extract, but not mitragynine, attenuated the severity of naloxone-precipitated morphine withdrawal symptoms. Neural signaling in the NAc and spontaneous motor activity were sensitive to morphine but not M. speciosa alkaloid extract. Therefore, treatment with the M. speciosa alkaloid extract may be useful for opiate addiction treatment program.
Topics: Alkaloids; Analgesics, Opioid; Animals; Behavior, Animal; Diarrhea; Male; Mice, Inbred ICR; Mitragyna; Morphine; Naloxone; Narcotic Antagonists; Nucleus Accumbens; Plant Extracts; Plant Leaves; Secologanin Tryptamine Alkaloids; Substance Withdrawal Syndrome
PubMed: 28687506
DOI: 10.1016/j.jep.2017.07.008 -
Fortschritte Der Neurologie-Psychiatrie Dec 2022Opiate addiction is common among offenders, and many opiate-dependent lawbreakers are treated in the correctional system according to § 64 STGB. While substitution...
Opiate addiction is common among offenders, and many opiate-dependent lawbreakers are treated in the correctional system according to § 64 STGB. While substitution treatment in prisons has become common practice, substitution treatment in forensic hospitals in the traditionally abstinence-oriented prison system is controversial and also varies from region to region. Basic data on this are lacking so far. The problem is discussed against the background of a current expert opinion case. Current figures from a large forensic hospital in Munich-East show that almost 30% of the patients are treated with substitutes (n=186). The problem of substitution treatment in the prison system is discussed.
Topics: Humans; Opiate Alkaloids; Analgesics, Opioid; Opioid-Related Disorders; Forensic Psychiatry; Hospitals; Opiate Substitution Treatment; Prisoners
PubMed: 35100637
DOI: 10.1055/a-1669-9033 -
Journal of the American Academy of... Jul 2022
Topics: Ambulatory Care; Dermatology; Health Care Surveys; Humans; Office Visits; Opiate Alkaloids; United States
PubMed: 34274414
DOI: 10.1016/j.jaad.2021.07.014 -
Journal of the Neurological Sciences Nov 2022Abuse of opiates, cocaine, and lipophilic inhalants (e.g., toluene) can damage brain myelin and cause acute toxic leukoencephalopathy (TL), but little is known about... (Review)
Review
OBJECTIVES
Abuse of opiates, cocaine, and lipophilic inhalants (e.g., toluene) can damage brain myelin and cause acute toxic leukoencephalopathy (TL), but little is known about recovery or prognosis in this condition. In light of the ongoing opiate epidemic in the United States, it is important to understand the natural history of patients who have acute neurological complications from illicit drug exposure. Our aim was to conduct a scoping review of the literature regarding prognosis in described cases of substance abuse-related TL.
METHODS
A strategic search of PubMed, Ovid, Cumulative Index to Nursing, and Allied Health Literature (CINAHL) databases yielded adult cases of acute TL from opiates, cocaine, or inhalants. Cases and case series were eligible for inclusion if they described acute leukoencephalopathy with a clear temporal association with opiate, cocaine, or inhalant abuse. Inclusion was contingent on availability of clinical descriptions until death or ≥ 4 weeks follow-up with neuroimaging consistent with TL.
RESULTS
Among 52 cases from 14 articles, 21 (40.4%) individuals died with mean time to death of 28.2 days; with mean follow-up of 12.8 months, 10 (19.2%) survived with no recovery, 17 (32.7%) had partial recovery, and 4 (7.7%) individuals had full recovery.
CONCLUSION
Substance abuse-related acute TL often has a poor prognosis, but partial or even full recovery is possible in a subgroup of individuals over months to years.
Topics: Adult; Female; Humans; United States; Substance-Related Disorders; Leukoencephalopathies; Illicit Drugs; Cocaine; Toluene; Prognosis; Opiate Alkaloids
PubMed: 36156344
DOI: 10.1016/j.jns.2022.120420 -
Journal of Neuroscience Research Jan 2022Poor sociability and aggressive behavior are key clinical features of opioid use disorders. The corticotropin-releasing factor (CRF) system may mediate behavioral...
Poor sociability and aggressive behavior are key clinical features of opioid use disorders. The corticotropin-releasing factor (CRF) system may mediate behavioral effects of substances of abuse but its implication in substance-induced social behavior deficits and outward-directed hostility remains largely unknown. CRF signaling is mediated by two receptor types, termed CRF and CRF . The present study aimed at understanding the role for the CRF receptor in social and aggressive behavior induced by withdrawal from repeated opiate administration. Thus, wild-type (CRF +/+), CRF receptor heterozygous (CRF +/-), and null mutant (CRF -/-) female and male mice were treated with saline or escalating doses of morphine (20-100 mg/kg, i.p.) during six consecutive days and tested in the three-chamber task for sociability (i.e., preference for an unfamiliar same-sex conspecific vs. an object) 7 days after the last administration. Moreover, aggressive biting behavior toward the unfamiliar conspecific was assessed during the three-chamber test. Opiate withdrawal disrupted sociability in CRF +/+ and CRF +/-, but not in CRF -/-, female mice, without affecting aggressive biting behavior in any genotype. In contrast, opiate withdrawal did not affect sociability but increased aggressive biting behavior in male mice, independently of CRF receptor-deficiency. Nevertheless, in opiate-withdrawn CRF +/+, but not CRF +/- and CRF -/-, male mice, sociability directly correlated with aggressive biting behavior, suggesting a role for the CRF receptor in hostility-linked social approach. These findings demonstrate the implication of the CRF receptor in social behavior deficits associated with repeated opiate administration and withdrawal, revealing a new potential target for the treatment of opioid use disorders.
Topics: Animals; Corticotropin-Releasing Hormone; Female; Male; Mice; Mice, Knockout; Opiate Alkaloids; Receptors, Corticotropin-Releasing Hormone; Social Behavior; Substance Withdrawal Syndrome
PubMed: 32725663
DOI: 10.1002/jnr.24697 -
World Neurosurgery Feb 2023Opioids are commonly prescribed for chronic pain before spinal surgery and research has shown an increased rate of postoperative adverse events in these patients.
BACKGROUND
Opioids are commonly prescribed for chronic pain before spinal surgery and research has shown an increased rate of postoperative adverse events in these patients.
OBJECTIVE
This study compared the incidence of 2-year subsequent surgical procedures and postoperative adverse events in patients undergoing lumbar fusion with or without 90-day preoperative opioid use. We hypothesized that patients using preoperative opioids would have a higher incidence of subsequent surgery and adverse outcomes.
METHODS
A retrospective cohort study was performed using the Optum Pan-Therapeutic Electronic Health Records database including adult patients who had their first lumbar fusion between 2015 and 2018. The daily average preoperative opioid dosage 90 days before fusion was determined as morphine equivalent dose and further categorized into high dose (morphine equivalent dose >100 mg/day) and low dose (1-100 mg/day). Clinical outcomes were compared after adjusting for confounders.
RESULTS
A total of 23,275 patients were included, with 2112 patients (10%) using opioids preoperatively. There was a significantly higher incidence of infection compared with nonusers (12.3% vs. 10.1%; P = 0.01). There was no association between subsequent fusion surgery (7.9% vs. 7.5%; P = 0.52) and subsequent decompression surgery (4.1% vs. 3.6%; P = 0.3) between opioid users and nonusers. Regarding postoperative infection risk, low-dose users showed significantly higher incidence (12.7% vs. 10.1%; P < 0.01), but high-dose users did not show higher incidence than nonusers (7.5% vs. 10.1%; P = 0.23).
CONCLUSIONS
Consistent with previous studies, opioid use was significantly associated with a higher incidence of 2-year postoperative infection compared with nonuse. Low-dose opioid users had higher postoperative infection rates than did nonusers.
Topics: Adult; Humans; Analgesics, Opioid; Retrospective Studies; Opiate Alkaloids; Pain, Postoperative; Postoperative Complications; Morphine; Opioid-Related Disorders
PubMed: 36396056
DOI: 10.1016/j.wneu.2022.11.044 -
Journal of Opioid Management 2021We sought to determine prescribing patterns for opioid analgesia following anterior cruciate ligament (ACL) reconstruction among age- and gender-stratified adolescents...
OBJECTIVE
We sought to determine prescribing patterns for opioid analgesia following anterior cruciate ligament (ACL) reconstruction among age- and gender-stratified adolescents in a nationally representative database.
DESIGN
A retrospective study.
SETTING
PearlDiver Patient Records.
PATIENTS, PARTICIPANTS
Outpatient opioid claims within 30 days of surgery were extracted. The patients were defined into age groups 10-14 ("younger") and 15-19 ("older"). A total of 1,139 patients were included in this study (536 female and 603 males) with 108 patients in the 10-14 age category and 1,034 patients in the 15-19 category.
MAIN OUTCOME MEASURE(S)
The primary study outcome measures the average number of opioid pills administered, average total morphine milligram equivalents (MMEs) prescribed, and the average prescription strength (MMEs/pill).
RESULTS
No difference was found in the average number of pills (p = 0.26) or normalized total MMEs (p = 0.312) prescribed by age group. Normalized total morphine equivalents per prescription was significantly lower in females than males (p = 0.005). Multivariate linear regression analysis demonstrated that increasing patient age was predictive of fewer total pills (p = 0.017), after accounting for gender.
CONCLUSIONS
There are age- and gender-based disparities in prescription patterns for adolescent ACL reconstruction. Our findings indicate that patients in the older age group on average received fewer pills than the younger age group, which consequently trended toward receiving higher total MMEs prescribed. This suggests that surgeons may be inadvertently overprescribing in the younger cohort. Additional studies that account for concurrent factors should be conducted to observe potentially similar trends.
Topics: Adolescent; Aged; Analgesics, Opioid; Anterior Cruciate Ligament Reconstruction; Female; Humans; Male; Opiate Alkaloids; Pain, Postoperative; Practice Patterns, Physicians'; Retrospective Studies
PubMed: 34533826
DOI: 10.5055/jom.2021.0664 -
Sleep Sep 2023Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found...
Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found that chronic opiate usage in humans and long-term opiate administration to mice significantly increased the number of detected hypocretin/orexin (Hcrt) neurons, decreased their size, and increased Hcrt level in the hypothalamus. We also found that opiates significantly decreased cataplexy in human narcoleptics as well as in narcoleptic mice and that cessation of locus coeruleus neuronal activity preceded and was tightly linked to cataplectic attacks in narcoleptic dogs. We tested the hypothesis that SXB produces changes similar to opiates and now report that chronic SXB administration significantly increased the size of Hcrt neurons, the reverse of what we had seen with opiates in humans and mice. Levels of Hcrt in the hypothalamus were nonsignificantly lower, in contrast to the significant increase in hypothalamic Hcrt level after opiates. SXB decreased tyrosine hydroxylase levels in the locus coeruleus, the major descending projection of the hypocretin system, also the reverse of what we saw with opioids. Therefore despite some similar effects on narcoleptic symptomatology, SXB does not produce anatomical changes similar to those elicited by opiates. Analysis of changes in other links in the cataplexy pathway might further illuminate SXB's mechanism of action on narcolepsy.
Topics: Humans; Mice; Animals; Dogs; Orexins; Sodium Oxybate; Cataplexy; Locus Coeruleus; Narcolepsy; Neurons; Opiate Alkaloids
PubMed: 37155728
DOI: 10.1093/sleep/zsad135 -
The Primary Care Companion For CNS... Mar 2023
Topics: Humans; Adolescent; Nicotine; Opiate Alkaloids; Social Stigma; Physicians
PubMed: 36946564
DOI: 10.4088/PCC.22br03358 -
Immunology Letters Nov 2020Integrated behavioral paradigms such as nociceptive processing coupled to anti-nociceptive responsiveness include systemically-mediated states of alertness, vigilance,... (Review)
Review
Emerging regulatory roles of opioid peptides, endogenous morphine, and opioid receptor subtypes in immunomodulatory processes: Metabolic, behavioral, and evolutionary perspectives.
Integrated behavioral paradigms such as nociceptive processing coupled to anti-nociceptive responsiveness include systemically-mediated states of alertness, vigilance, motivation, and avoidance. Within a historical and cultural context, opium and its biologically active compounds, codeine and morphine, have been widely used as frontline anti-nociceptive agents. In eukaryotic cells, opiate alkaloids and opioid peptides were evolutionarily fashioned as regulatory factors in neuroimmune, vascular immune, and systemic immune communication and auto-immunoregulation. The significance of opioidergic regulation of immune function was validated by the identification of novel μ and δ opioid receptors on circulating leukocytes. The novel μ3 opioid receptor subtype has been characterized as an opioid peptide-insensitive and opiate alkaloid-selective G protein-coupled receptor (GPCR) that is functionally linked to the activation of constitutive nitric oxide synthase (cNOS). Opioid peptides stimulate granulocyte and immunocyte activation and chemotaxis via activation of a novel leukocyte δ2 receptor subtype. However, opiate alkaloid μ3 receptor agonists inhibit these same cellular activities. Opiate coupling to cNOS and subsequent production and release of mitochondrial nitric oxide (NO) suggests an evolutionary linkage to similar physiological events in prokaryotic cells. A subpopulation of immunocytes from Mytilus edulis and Leucophaea maderae and human granulocytes respond to low opioid concentrations, mediated by the adherence-promoting role of (D-Ala2-D-Met5)-enkephalinamide (DAMA), which is blocked by naloxone in a dose-dependent manner. Neutral endopeptidase 24.11 (NEP), or enkephalinase (CD10), is present on both human and invertebrate immunocytes. Alkaloids, including morphine, are found in both prokaryotic and eukaryotic cells and may have evolved much later in evolution through horizontal gene transfer. It is possible that opioid-mediated regulatory activities were conserved and elaborated during evolution as the central nervous system (CNS) became immunologically isolated by the blood-brain barrier. Thus, opioid receptor coupling became significant for cognitive and behavioural processes. Although opioid peptides and alkaloids work synergistically to suppress nociception, they mediate different actions in immune surveillance. Increased understanding of the evolutionary development of opioid receptors, nociceptive and anti-nociceptive pathways, and immunomodulation may help in the understanding of the development of tolerance to the clinical use of opiates for pain management. The significance of endogenous morphine's importance to evolution can be ascertained by the number of physiological tissues and systems that can be affected by this chemical messenger mechanism, which transcends pain. An integrated review is presented of opioid and opiate receptors, immunomodulation, and pain associated with inflammation, from an evolutionary perspective.
Topics: Animals; Behavior; Biological Evolution; Humans; Immunity; Immunomodulation; Inflammation; Morphine; Nitric Oxide; Opioid Peptides; Pain; Receptors, Opioid
PubMed: 32827633
DOI: 10.1016/j.imlet.2020.08.007